Patients cured of cryptococcal meningitis did not respond to immunization with cryptococcal polysaccharide either as measured by serum antibody or presence of circulating blood lymphocytes (PBL) which spontaneously secreted anticryptococcal antibody. Response to type III pneumococcal polysaccharide was normal by both parameters, as was immunoglobulin secretion by mitogen-stimulated PBL. These patients have long-lasting specific tolerance to polysaccharide from the infecting fungus. Rabbit IgG antibody to the capsular polysaccharide of type D Cryptococcus neoformans has affinity for both the xylose and glucuronate side chains but not the mannan core. Computer modeling of the polysaccharide structure offered an explanation for these findings. An experimental model and mode of analysis was devised to show that the often impuned flucytosine in vitro susceptibility test correlated with in vivo protection of mice infected with Candida albicans.